Caratterizzazione morfologica e molecolare di tumori stromali gastrointestinali (GIST) sincroni in popolazione adulta non sindromica

Purpose: Gastrointestinal stromal tumors (GIST) are commonly regarded as solitary tumors, and the occurrence of multiple lesions is considered an extraordinary event restricted to pediatric GISTs and rare hereditary conditions. Beyond these well-defined situations, the presentation of multiple synchronous lesions is commonly viewed as the result of the metastatic spreading of a single primitive GIST. Based on this axiom, patients with multifocal disease are by default classified as advanced stage and treated as such. Whether, indeed, the detection of several lesions in sporadic adult GIST patients may be suggestive of phenomena of tumor multiplicity still needs to be clarified. Experimental design: From a multicentric series of 442 consecutive cases, 79 of which diagnosed with advanced disease, we selected 5 patients who presented up to 4 distinct GIST nodules. Five additional cases with silimar characteristics were retrieved by collaborators. Clonal relationships of the synchronous lesions was assessed by comparing c-KIT/PDGFRA mutation and microsatellite pattern . Results: An independent origin of the syncronous lesions was assessed in 6 out of the 10 cases analyzed. Interestingly, in one patient one of the lesions stemmed from the peritoneum, ordinarily regarded as a site of metastasis. Conclusions: Our data indicate that a significant fraction of GIST patients with multifocal manifestations are actually affected by multiple primary GISTs, suggesting that mesenchymal cells of these subjects are somehow primed to transformation Thus, in the presence of multifocal GIST manifestations, an accurate characterization of the different tumor localizations should be taken into account for a proper patient staging and planning of the therapy.